The mouse core has been established to assist PPG member laboratories in the design, production and characterization of transgenic and knockout mouse strains. The mouse core will be responsible for all aspects of mouse engineering and will provide scientific advice on issues relating to mouse genetics and biology and to cancer modeling. Details on the construction of other mouse lines can be found in each of the accompanying proposals. We present the engineering of such mutant mouse strains as illustrative examples. These strains are the conditional PTEN knockout and the probascin-driven transgenic line. Specifically, for the production of transgenic mice, the facility will (i) maintain the core colony needed for production of the embryos and foster females, (ii) purify transgene inserts for microinjection, (iii) perform pronuclear microinjections, and (iv) conduct oviduct transfers, monitor births, and confirm transgenic founders. For the gene targeting experiments, the core responsibilities will be to (i) assist investigators in the design and construction of targeting vectors, (ii) conduct the ES transfections, selections, and clone picking and freezing, (iii) perform blastocyst microinjections of mutant ES cells, and (iv) perform uterine transfers and monitor chimera formation.